The present invention relates to a prosthesis for a blood vessel, which is composed of an expanded porous polytetrafluoroethylene (i.e., a stretched polytetrafluoroethylene) tube manufactured by stretching process using a polytetrafluoroethylene (PTFE) as a raw material. And more particularly to a prosthesis for a blood vessel which is excellent in mechanical properties and histocompatibility and exhibits good patency even when its inner diameter is as small as less than 6 mm, particularly at most 5 mm, more particularly at most 4 mm. The prosthesis for a blood vessel includes a vascular prosthesis, a covering material of a covered stent, etc. and may hereinafter be referred to as xe2x80x9cvascular prosthesisxe2x80x9d which is representative thereof.
Prostheses for blood vessels typified by vascular prostheses are used as a substitute for a lesion part of a vital blood vessel, a prosthesis for a defective part, a bypass for going around the lesion part to maintain blood flow, a conduit for shunting an artery to a vein, etc. As materials for the vascular prostheses, are used, for example, porous PTFE tubes manufactured by a stretching process, woven fabrics and knitted webs of polyester fibers, etc. The vascular prostheses are required to have antithrombogenicity and histocompatibility, since blood flows through their lumina, and they are often implanted in vivo for use by substitution implantation, bypass implantation or the like.
Among the vascular prostheses, a vascular prosthesis composed of an expanded porous PTFE tube (hereinafter referred to as xe2x80x9ca porous PTFE vascular prosthesisxe2x80x9d) is excellent in antithrombogenicity and histocompatibility and hence used widely. The features of the porous PTFE vascular prosthesis reside in that first of all the PTFE itself of a material is excellent in antithrombogenicity. Therefore, the porous PTFE vascular prosthesis is excellent in antithrombogenicity.
Second, the porous PTFE vascular prosthesis has a fine fibrous structure comprising a number of fine fibers (i.e., fibrils) and nodes interconnected with one another by said fibrils. This fine fibrous structure forms a porous structure composed of communicable pores. The porous structure composed of such a fine fibrous structure itself is excellent in affinity for the vital tissue, and the vital tissue penetrates into the porous structure, whereby healing by organization is easy to facilitate.
Third, in the porous PTFE vascular prosthesis, the porous structures such as average fibril length, average pore diameter and porosity, and the forms such as inner diameter and wall thickness may be easily changed by controlling production conditions such as draw ratio upon stretching. Therefore, the porous PTFE vascular prosthesis can cope with various requirements.
As described above, the porous PTFE vascular prosthesis is excellent in antithrombogenicity and histocompatibility and exhibits excellent properties compared with a polyester fiber-made vascular prosthesis. However, although the expanded porous PTFE vascular prosthesis has such excellent properties, when it is provided as a vascular prosthesis having an inner diameter as small as less than 6 mm, particularly at most 5 mm, it occludes in a relatively short period of time after implantation into the vital body so that any good patency cannot be achieved. When occlusion is repeated, the vascular prosthesis must be replaced on that occasion. Therefore, the porous PTFE vascular prosthesis is only put to practical use in a region of the inner diameter of at least 6 mm.
Various techniques have heretofore been proposed in order to improve the patency of the porous PTFE vascular prosthesis. These techniques are roughly divided into (1) a method in which the surface of the porous PTFE vascular prosthesis is modified by, for example, coating the surface with an antithrombogenic substance, thereby improving the antithrombogenicity and histocompatibility thereof, and (2) a method in which the fine fibrous structure constituting the porous structure is modified or optimized, thereby improving the physical properties and/or the histocompatibility thereof. Among these techniques, the method of modifying the surface of the porous PTFE vascular prosthesis is not sufficient in the improving effect by itself, and it is hence desirable to practice it in combination with the method of modifying or optimizing the fine fibrous structure.
The method of modifying or optimizing the fine fibrous structure includes a method in which the average fibril length (distance between nodes) in the fine fibrous structure is lengthened to enlarge the pore diameter of the vascular prosthesis for the purpose of enhancing the penetrability of the vital tissues into the porous structure after implantation of the porous PTFE vascular prosthesis for facilitating healing by organization. Specifically, in Journal of VASCULAR SURGERY, Vol. 11, No. 6, p. 838-845, June (1990), it is reported that a porous PTFE vascular prosthesis, the average fibril length of which has been enlarged to 30 to 60 xcexcm, particularly about 60 xcexcm, exhibits a marked healing effect compared with a generally marketed porous PTFE vascular prosthesis the average fibril length of which is about 10 to 30 xcexcm.
Japanese Patent Application Laid-Open No. 135894/1975 has proposed a porous PTFE vascular prosthesis in which the length of fibrils has been controlled to longer than 5 xcexcm, preferably longer than 5 xcexcm, but not longer than 1000 xcexcm, more preferably 20 to 100 xcexcm.
According to the result of an implantation experiment by the present inventors, however, it has been found that no sufficient patency is achieved only by enlarging the average fibril length in a small diameter porous PTFE vascular prosthesis having an inner diameter as small as less than 6 mm. The analysis of the reason for it has revealed the following fact.
First, in an expanded porous PTFE tube, the fibrils are strongly oriented in the axial direction of the tube by stretching. Therefore, the rigidity against compression in axial and radial directions of the tube is low though the tensile strength in the axial direction of the tube is high. When the draw ratio upon stretching is made high to enlarge the average fibril length, the rigidity against compression in the axial and radial directions of the tube is further lowered.
When the porous PTFE vascular prosthesis is implanted at a site to which a bending load is applied, a site pressured from surroundings, a site low in blood pressure such as a vein or the like, mechanical pressure is given to the prosthesis, and the prosthesis to become easy constricted. In addition, when the surrounding vital tissue adhered to the outer surface of the porous PTFE vascular prosthesis, or the vital tissue penetrated into the porous wall thereof contracts, the porous PTFE vascular prosthesis tends to be shortened correspondingly. When the porous PTFE vascular prosthesis undergoes deformation such as constriction or shortening, the patency after the implantation into the vital body markedly drops. Such a problem becomes particularly marked when the average fibril length is lengthened, the wall thickness is thinned, or the inner diameter is made small. More specifically, when it is intended to increase the draw ratio upon stretching to enlarge the pore diameter (fibril length) for the purpose of enhancing the affinity for the vital tissue, there arises a problem that the rigidity of the expanded porous PTFE tube is further lowered to fail to apply it to a vascular prosthesis.
In order to solve the problem that the rigidity of the porous PTFE vascular prosthesis against compression in the axial and radial directions thereof is low, there has heretofore been proposed, for example, a method in which reinforcing filaments are wound in the form of a coil or ring around the outer surface of an expanded porous PTFE tube (Japanese Patent Publication Nos. 37734/1985 and 56619/1985). In the method in which the reinforcing filaments are wound around the outer surface of the expanded porous PTFE tube, the reinforcing filaments are wound at a fixed interval to be bonded. Therefore, a difference in rigidity is made between portions reinforced with the filament and portions not reinforced. Accordingly, when the interval at which the reinforcing filaments are wound is in some measure great, the vascular prosthesis is deformed as if it is folded at the portions of the wound reinforcing filaments as flucrums when the vascular prosthesis is bent. As a result, constriction occurs.
It is necessary to closely wind the reinforcing filaments when it is intended to enhance strength against internal pressure, or in order to prevent buckling against pressure from surroundings or bending. When the reinforcing filaments are closely wound, however, penetration of the vital tissue into the porous wall from the surroundings is inhibited by the reinforcing filaments to slow the healing by organization. In addition, the flexibility of the expanded porous PTFE tube is impaired. Therefore, the handling itself becomes difficult. The mere close winding of the reinforcing filaments scarcely achieves an effect to enhance the resistance to the shortening in the axial direction of the tube. Therefore, the shortening of the vascular prosthesis in the axial direction thereof following the contraction of the vital tissue adhered to the outer surface of the vascular prosthesis, or the vital tissue penetrated into the porous wall thereof, cannot be prevented. More specifically, the vascular prosthesis composed of the expanded PTFE tube wounded with the reinforcing filaments causes a phenomenon that it is shortened in the axial direction thereof, it is bended to form thrombus, or the vital tissue formed on the inner wall of the vascular prosthesis peals off or undergoes hypertrophy, thereby it occludes in a short period of time.
In addition, in the vascular prosthesis composed of the expanded PTFE tube wounded with the reinforcing filaments, the reinforcing filaments were an obstacle when suturing the vascular prosthesis to a vital blood vessel. It is therefore necessary to remove the reinforcing filaments at the sutured part. Since the porous PTFE vascular prosthesis is partially broken or deformed by this removing operation itself, thrombus easily forms at the sutured part, the pseudointima of the vital tissue topically undergoes pealing off or hypertrophy. Since rigidity is insufficient at the portion from which the reinforcing filaments have been removed, the shortening of the vascular prosthesis in the axial direction thereof caused by the vital tissue adhered to the outer surface of the vascular prosthesis or the vital tissue penetrated into the porous wall, cannot be prevented. Therefore, the vascular prosthesis is compressed and deformed in the radial direction thereof or contracted in the axial direction thereof, leading to its occlusion in a short period of time.
There has heretofore been proposed a method in which porosity is controlled to at most 60% while enlarging the pore diameter by increasing the draw ratio upon stretching, thereby preventing lowering of compressive rigidity in the axial direction of the tube (Japanese Patent Application Laid-Open No. 277273/1994). According to this method, a porous PTFE vascular prosthesis enlarged in pore diameter can be provided without lowering the rigidity. Since this porous PTFE vascular prosthesis is low in porosity, however, the effect to facilitate the penetration of the vital tissue into the porous wall by the enlarged pore diameter is not sufficiently achieved, and so it tends to occlude in a short period of time. In addition, when the porosity is low, the area ratio of the PTFE resin at the luminal surface increases, so that an anchoring effect by the junction of a pseudointima formed on the luminal surface after implantation to the tissue penetrated into the porous wall becomes insufficient. As a result, the pseudointima is easy to be pealed off by blood flow, resulting in occlusion.
Second, the mere enlargement of the pore diameter of the expanded porous PTFE tube enhances the communicating ability of pores to facilitate the penetration of the vital tissue through the outer surface thereof, but on the other hand, exudation of blood and/or serum from the outer surface is easy to occur when the communicating ability of the pores is enhanced in excess, which is the cause that shows a strong tendency to cause adhesion of surrounding tissue to lead to occlusion.
As a means for avoiding the excessive communicating ability of the pores caused by the enlarged pore diameter, there is considered a method in which the structures of fibrils and nodes forming the fine fibrous structure are improved. However, the structure of the fibrils is as simple as a fine filament connecting nodes with each other. Therefore, it can be only expected that the communicating ability of the pores is slightly changed by, for example, enlarging the fibril diameter or raising the fibril density. However, it is extremely difficult to control the fibril diameter and fibril density while lengthening the average fibril length to enlarge the pore diameter.
On the other hand, It has been known that the structure of the nodes can be controlled to same extent. For example, Japanese Patent Publication No. 15022/1995 discloses a process comprising using an extrusion tip or die having a spiral groove in an extrusion process to extrude PTFE into a tube and then stretching the PTFE tube, thereby producing a expanded porous PTFE tube in which substantially all nodes are oriented at an angle of 85xc2x0 to 15xc2x0 to the axis of the tube. Examples of this publication show not only those having an average fibril length as short as 10 to 22 xcexcm, but also those having an average fibril length as long as 76 xcexcm.
However, the expanded porous PTFE tubes described in this publication are different from the conventional products only in that the nodes are oriented at one or plural angles to the axis thereof, and the fine fibrous structure itself is unchanged. More specifically, this process is not basically a process devised for controlling the communicating ability of the pores. Therefore, exudation of blood and/or serum from the outer surface due to the enlarged pore diameter can be reduced. Accordingly, this process does not contribute to the improvement in patency.
It is an object of the present invention to provide a prosthesis for a blood vessel, which is manufactured from an expanded porous PTFE tube having a fine fibrous structure comprising fibrils and nodes connected with one another by said fibrils, has a long average fibril length, a large pore diameter, a high porosity, a excellent effect to facilitate penetration into the vital tissue and sufficient rigidity against compression in axial and radial directions thereof even without reinforcing it and is markedly improved in patency after its implantation into a vital body.
Another object of the present invention is to provide a prosthesis for a blood vessel, which is manufactured from an expanded porous PTFE tube having a small diameter in particular and is markedly improved in patency after its implantation into a vital body.
The present inventors have carried out an extensive investigation with a view toward achieving the above objects. As a result, it has been found that even a prosthesis for a blood vessel manufactured from an expanded porous PTFE tube having an average fibril length as long as at least 40 xcexcm and a porosity as high as at least 70% exhibits excellent patency over a long period of time after its implantation so far at the tube requires a load of a certain value or higher for compressing it in its axial direction and produces a resistant force of a certain value or higher at that time.
It has been further found that when nodes in the fine fibrous structure of the above-described expanded porous PTFE tube have a particular structural feature, exudation of blood and/or serum from its luminal surface can be effectively prevented even when the tube has a large pore diameter and a high porosity. The present invention has been led to completion on the basis of these findings.
According to the present invention, there is thus provided a prosthesis for a blood vessel, which is manufactured from an expanded porous polytetrafluoroethylene tube having a fine fibrous structure comprising fibrils and nodes connected with one another by said fibrils, wherein the tube has the following features:
(A) the average fibril length being at least 40 xcexcm;
(B) the porosity being at least 70%;
(C) a load required for compressing the tube by 10% in its axial direction at a strain rate of 100%/min being at least 10 gf; and
(D) a resistant force per unit sectional area of the tube produced upon the 10% compression being at least 1.0 gf/mm2.